Clinical Characteristics Of Systemic Lupus Erythematosus Research Articles

Study on the expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with Treg cells.

We initially explored the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T (Treg) cells by detecting the lncRNA expression profiles in patients with systemic lupus erythematosus (SLE), then analyzed the correlation between Treg-related lncRNAs and the clinical features of SLE patients, predicting the mechanism by which lncRNAs regulate the differentiation and development of Treg cells, and provided new ideas for the treatment of SLE. Peripheral blood of 9 active SLE patients were collected and mononuclear cells (PBMCs) were extracted; the lncRNA expression profiles of PBMCs were analyzed by whole transcriptome sequencing. Nine healthy people were used as controls to screen the differentially expressed lncRNAs, to analyze the correlation between lncRNAs and Treg cell number. Pearson test was used to analyze the correlation between lncRNAs and the number of Treg cell, and the correlation between Treg-associated lncRNA and SLEDAI score, ESR, C3, and C4 in SLE patients. The targeted genes of Treg-associated lncRNAs were predicted with miRcode and Targetscan databases and coexpression network. There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs (p < 0.05) and 106 lowly expressed lncRNAs (p < 0.05). The expression of ANKRD44-AS1 (r = 0.7417, p = 0.0222), LINC00200 (r = 0.6960, p = 0.0373), AP001363.2 (r = 0.7766, p = 0.0138), and LINC02824 (r = 0.7893, p = 0.0114) were positively correlated with the number of Treg cell, and the expression of AP000640.1 (r = - 0.7225, p = 0.0279), AC124248.1 (r = - 0.7653, p = 0.0163), LINC00482 (r = - 0.8317, p = 0.0054), and MIR503HG (r = - 0.7617, p < 0.05) were negatively correlated with the number of Treg cell. Among these Treg-associated lncRNAs, the expression of LINC00482 (r = - 0.7348, p < 0.05) and MIR503 HG (r = - 0.7617, p < 0.05) were negatively correlated with C3. LINC00200, ANKRD44 - AS1, and AP000640.1 related to Treg cells regulate the expression of signal transducer and activator of transcription 5 (STAT5), phospholipase D1 (PLD1), homeodomain-only protein X (HOPX), and runt-related transcription factor 3 (RUNX3) through competitive binding of miRNA or trans-regulatory mechanism, thereby regulating the differentiation and development of Treg cell. The lncRNA expression profiles were changed in SLE patients, the differentially expressed lncRNAs were associated with abnormal number and function of Treg cells in SLE, and Treg-associated lncRNAs were associated with SLE-disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Treg cell function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism. Key points • Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and systems. lncRNAs may affect Treg cells function by regulating genes expression, which may be an important pathogenesis of SLE. • This study, taking SLE as an example, preliminarily analyzed the correlation between lncRNA and Treg cells in SLE patients, analyzed the correlation between Treg-related lncRNA and the clinical characteristics of SLE, and speculated that lncRNA could regulate the differentiation and development of Treg cells through competitive combination with miRNA or trans-regulatory mechanisms. • It is possible to target epigenetic therapy for SLE.

Novel polymorphism of IFI44L associated with the susceptibility and clinical characteristics of systemic lupus erythematosus in a Chinese population

Interferon-inducible 44 like (IFI44L) is a newly discovered gene which has been reported to associate with the susceptibility of some infectious diseases, but there is no data on IFI44L SNP polymorphism associated with Systemic lupus erythematosus (SLE). In this study, we aimed to evaluate the association of IFI44L rs273259 polymorphism with the susceptibility and clinical characteristics of SLE in a Chinese population. 576 SLE patients and 600 controls were recruited in this case-control study. Blood DNA was extracted and IFI44L rs273259 polymorphism was detected by TaqMan SNP Genotyping Assay Kit. The expression levels of IFI44L in Peripheral blood mononuclear cells were detected by RT-qPCR. The DNA methylation levels of IFI44L promoter were detected by bisulfite pyrosequencing. The genotype and allele frequencies of IFI44L rs273259 in SLE patients have a significantly difference compared to healthy controls (P<0.001). The genotype AG (vs. AA: OR=2.849; P<0.001) and the allele G (vs. A: OR=1.454; P<0.001) were associated with increased susceptibility of SLE. IFI44L rs273259 polymorphism was associated with clinical characteristics of SLE including malar rash (P<0.001), discoid rash (P<0.001), lupus nephritis (P<0.001) and anti-Smith antibodies (P<0.001). The expression levels of IFI44L were most significantly increased in genotype AG than genotype AA and GG (P<0.01). The DNA methylation levels of IFI44L promoter were most significantly decreased in genotype AG than genotype AA and GG (P<0.01). Our results indicate novel polymorphism of IFI44L rs273259 was associated with the susceptibility and clinical characteristics of SLE in the Chinese population.

A Flare Risk Index Informed by Select Immune Mediators in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is marked by immune dysregulation linked to varied clinical disease activity. Using a unique longitudinal cohort of SLE patients, this study sought to identify optimal immune mediators informing an empirically refined flare risk index (FRI) reflecting altered immunity prior to clinical disease flare. Thirty-seven SLE-associated plasma mediators were evaluated by microfluidic immunoassay in 46 samples obtained in SLE patients with an imminent clinical disease flare (preflare) and 53 samples obtained in SLE patients without a flare over a corresponding period (pre-nonflare). SLE patients were selected from a unique longitudinal cohort of 106 patients with classified SLE (meeting the American College of Rheumatology 1997 revised criteria for SLE or the Systemic Lupus International Collaborating Clinics 2012 revised criteria for SLE). Autoantibody specificities, hybrid SLE Disease Activity Index (hSLEDAI) scores, clinical features, and medication usage were also compared at preflare (mean ± SD 111 ± 47 days prior to flare) versus pre-nonflare (99 ± 21 days prior to nonflare) time points. Variable importance was determined by random forest analysis with logistic regression subsequently applied to determine the optimal number and type of analytes informing a refined FRI. Preflare versus pre-nonflare differences were not associated with demographics, autoantibody specificities, hSLEDAI scores, clinical features, nor medication usage. Forward selection and backward elimination of mediators ranked by variable importance resulted in 17 plasma mediator candidates differentiating preflare from pre-nonflare visits. A final combination of 11 mediators best informed a newly refined FRI, which achieved a maximum sensitivity of 97% and maximum specificity of 98% after applying decision curve analysis to define low, medium, and high FRI scores. We verified altered immune mediators associated with imminent disease flare, and a subset of these mediators improved the FRI to identify SLE patients at risk of imminent flare. This molecularly informed, proactive management approach could be critical in prospective clinical trials and the clinical management of lupus.

Single Nucleotide Polymorphism rs6445975 in the PXK Gene Is Correlated with Susceptibility and Clinical Characteristics of Systemic Lupus Erythematosus.

Background:Recently, genome-wide association studies (GWAS) have discovered several single nucleotide polymorphisms (SNPs) and loci associated with the risk of systemic lupus erythematosus (SLE). rs6445975 (T>G; intronic variant) polymorphism in the PXK gene is one of these loci. However, there was an inconsistency between the results of replicative studies on European and Asia ancestry. This study aimed to assess the possible association between rs6445975 polymorphism with SLE risk in the Iranian population.Methods:Genotype and allele distribution of rs6445975 polymorphism were investigated in 110 patients with SLE and 115 healthy controls in Isfahan University of Medical Sciences, Isfahan, Iran in 2019 via real-time PCR high resolution melting method (HRM).Results:GG and TG genotypes, but not TT genotype, were associated with increased risk of SLE (GG vs TT; OR= 7.538; 95%CI [3.47, 17.066] and TG vs TT; OR=2.21; 95%CI [1.06, 4.72]). Inheritance analysis revealed that TG + GG was correlated with the increased risk of SLE disease in the dominant model (OR=3.928; 95%CI [2.056, 7.74]). Moreover, subjects with the G allele were more frequently affected with SLE than individuals with the T allele (OR= 3.55; 95%CI [2.37, 5.36]). The G allele in patients was correlated with serum concentration of CRP, ESR, anti-dsDNA antibody, C3, and C4 and presentation of some clinical manifestations such as kidney involvements and skin lesions (P<0.05).Conclusion:Our findings suggest a substantial association between rs6445975 polymorphism in the PXK gene with susceptibility and clinical characteristics of SLE in the Iranian population.

Differentially methylation of IFI44L gene promoter in Iranian patients with systemic lupus erythematosus and rheumatoid arthritis.

Systemic lupus erythematosus(SLE) and rheumatoid arthritis(RA) are multisystemicautoimmune diseases with multifactorial nature. Considering the limitations of the current conventional serological tests for the diagnosis of these diseases, researchers strive to find more new valid biomarkers. Sixty-nine patients with SLE, 63 patients with RA, and 71 healthy controls were recruited to evaluate the methylation level of interferon-induced protein 44-like(IFI44L) promoter. Quantitative methylation of the promoter region of the IFI44L gene was measured in extracted DNA of peripheral blood mononuclear cells (PBMCs) with methylation-quantification endonuclease-resistant DNA (MethyQESD) method. Our findings unveiled a drastic hypomethylation of IFI44L promoter in SLE and RA patients compared with healthy volunteers (mean: 40.23% ± 64.54%, 35.19% ± 24.09%, and 71.98% ± 23.83%, respectively; P < 0.001 for both SLE and RA). In comparison between SLE and RA patients with the control group, IFI44L promoter methylation had a sensitivity of 81.15% and 84.12%, respectively, and specificity was 76.05%. The promoter methylation level was not meaningfully different between SLE and RA patients (P = 0.267). Moreover, our analysis revealed that the methylation level of the IFI44L promoter was not significantly different between SLE disease activity and renal involvements (P > 0.05). While RA patients with a higher concentration of CRP had a lower DNA methylation level (P = 0.023). The methylation level of IFI44L promoter was lower in PBMCs of Iranian patients with SLE and RA than that in the control group. Furthermore, DNA methylation level of the IFI44L promoter had a negative correlation with RA disease activity. However, there was not a significant association with the clinical characteristics of SLE.

A cross-sectional study of clinical and laboratory characteristics of systemic lupus erythematosus in tribal region of Jharkhand at RIMS, Ranchi.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown etiology, mainly affecting female of child-bearing age group. Clinical scenario of SLE is not well defined in east region of India, especially in tribal region of Jharkhand. This article is mainly focused on clinical and laboratory characteristics of SLE in tribal region of Jharkhand. This was an analytical cross-sectional single-centered study conducted at RIMS, Ranchi, a tertiary care center of Jharkhand, between November 2020 and October 2021. A total 50 patients were diagnosed as SLE based on Systemic Lupus International Collaborating Clinics criteria. Forty-five (90%) of patients in our study were female, with female to male ratio of 9:1. The mean age of presentation was 26.78 ± 8.12. Constitutional symptoms were found in 96% of patients, followed by anemia in 90% of patients. Renal involvement was found in 74% of patients, followed by polyarthritis (72%), malar rash (60%), and neurological manifestations (40%). Anti-nuclear antibody, anti-dsDNA, and anti-Smith antibodies were found positive in 100%, 84%, and 80% of patients, respectively. Clinical characteristics of SLE as per our study would help the health care professionals in this region to identify the disease at early stage and initiate appropriate treatment.

Clinical utility of urinary soluble CD163 in evaluation of lupus nephritis patients

Aim of the workTo assess urinary soluble CD163 (sCD136) in systemic lupus erythematosus (SLE) patients compared to healthy controls. In addition to determine its association with different SLE clinical features, laboratory investigations and pathological indices focusing on those suggest renal disease activity. Patients and methodsThe study included 58 SLE patients and 30 controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active lupus nephritis (ALN) (renal SLEDAI ≥ 4) and no-renal activity (NRA) SLE patients (renal SLEDAI = 0). Urinary sCD163 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Urine values were normalized to urinary creatinine excretion. Renal biopsies were performed in 21 ALN patients. ResultsThey were 54 females and 4 males with a mean age 31.8 ± 9.1 years and disease duration 6.2 ± 4.8 years. They were 31 with ALN and 27 NRA SLE patients. Urinary sCD163 level was significantly higher in SLE patients (1.85 ± 0.3) than controls (0.5 ± 0.36, p < 0.001). In ALN, it was significantly higher (2.91 ± 2.52) compared to NRA SLE patients (0.64 ± 0.38) and controls (p < 0.001 in both). The optimum cut-off value above which normalized urinary sCD136 can predict renal activity was > 0.82 with sensitivity of 90.3%, specificity of 88.89%, p < 0.001. Urinary sCD163 significantly correlated with renal (r = 0.75, p < 0.001) but not with extra-renal SLEDAI. It correlated with activity index of renal biopsy (r = 0.46, p = 0.038). ConclusionUrinary sCD163 is a potential biomarker for LN activity. Its level is associated with clinical features, laboratory investigations and pathological indices that indicate renal disease activity.

Association of CD14 genetic variants and circulating level with systemic lupus erythematosus risk in Egyptian children and adolescents.

Aim: To demonstrate whether sCD14 and CD14 (rs2569190 A/G and rs2569191 C/T) genetic variants are associated with systemic lupus erythematosus (SLE) risk, for the first time, in Egyptian pediatrics and adolescents. Materials & methods: sCD14 concentrations were determined in plasma of 95 SLE cases and 98 healthy controls using ELISA assay. Genotyping was performed using TaqMan technology. Results: sCD14 levels were elevated in SLE. Individuals with T, CTand TTgenotypes in rs2569191 were of significant risk (odds ratio =1.471-2.035, 95% CI=1.138-3.471) and those with combined CT+TTand haplotype GTwere of higher risk of SLE (odds ratio =1.660-1.758, 95% CI=1.003-3.106, p<0.05). sCD14 levels and CD14 polymorphism were not correlated with SLE clinical and laboratory features. Conclusion: In SLE, sCD14 levels are associated with rs2569190 A/G. Genotype CT+TTin rs2569191 C/T and haplotype GTare associated with SLE risk in Egyptian pediatric and adolescents.

CIITA gene polymorphism (rs3087456) in systemic lupus erythematosus and rheumatoid arthritis: A population-based cohort study.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co-activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456localized in the gene promoter region (-168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations.

Increased TIM-3+PD-1+ NK cells are associated with the disease activity and severity of systemic lupus erythematosus

It is well established that natural killer (NK) cells are dysregulated in systemic lupus erythematosus (SLE) patients. However, the functions of NK cells and the mechanisms regulated by them in SLE remain incompletely understood. Patients with SLE were recruited from The First Affiliated Hospital of Nanchang University, and their clinical characteristics and treatments were recorded. The expression levels of T cell immunoglobulin mucin-3 (TIM-3) and programmed cell death protein 1 (PD-1) on NK cells were examined using flow cytometry. The correlations between the increase in TIM-3+PD-1+ NK cells in the SLE patients and clinical traits, including inflammatory markers, auto-antibodies, disease activity and severity of SLE, were examined. The TIM-3+NK cells, PD-1+NK cells and TIM-3+PD-1+ NK cells were significantly increased in the SLE patients. The increase in TIM-3+PD-1+ NK cells in the patients with SLE was associated with erythrocyte sedimentation rate, C-reactive protein, anti-double stranded DNA, anti-ribosomal P, SLE disease activity index and clinical features. The frequency of TIM-3+PD-1+NK cells in SLE patients with a cardiovascular disease (CVD) was significantly lower than that in SLE patients without a CVD. Moreover, the increased TIM-3+PD-1+ NK cells were significantly decreased in SLE patients following treatment. The present study suggested that the increased TIM-3+PD-1+ NK cells were associated with the disease activity and severity of SLE and may play a role in SLE pathogenesis.

RNA receptors, TLR3 and TLR7, are potentially associated with SLE clinical features.

The influence of intracellular Toll-like-receptors (TLR), recognized as nucleic acid sensors, in the immunopathogenesis of systemic lupus erythematosus (SLE) is increasingly explored. Yet, the results of both functional and genetic studies remain conflictual. We evaluated the association between TLR3 and TLR7 genes selected variants and SLE and investigated the possible relationship with clinical and serological parameters. Then, we studied the genetic expression of these receptors, and if the TLR7 gene evades X chromosome inactivation (XCI). Our study covers 106 cases and 200 controls, genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TLR3 and TLR7 expression level was assessed by qPCR carried, respectively, on renal tissues and PBMC, and methylation status was evaluated by methylation-specific PCR. Results were statistically analysed using Shesis software, χ2 , and Mann-Whitney test. Significant associations with SLE susceptibility were found for the TLR3 rs3775291, rs5743305 and rs3775294 polymorphisms. Further subgroup analysis, TLR3 rs3775291 and rs3775294 polymorphisms were significantly associated with lupus nephritis (LN) and even correlate with the presence of auto-antibodies binding RNA molecules. SLE and LN were more common in men with rs3853839-G variant within TLR7 gene versus those carrying the C allele. Moreover, the role of the G allele in the TLR7 expression up-regulation was confirmed. However, gene expression analysis showed no significant differences in TLR3 and TLR7 mRNA levels between LN patient biopsies and healthy tissues (p>.05). When comparing patients and controls, no statistical difference was observed in XCI pattern. Otherwise, notable associations were raised between TLR3 and TLR7 gene variants and clinical and serological lupus features pointing towards the role of genetic background in the physiopathogenesis of the disease.

Association of tumor necrosis factor alpha-induced protein 3 gene polymorphism and systemic lupus erythematosus

Background Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) is a negative regulator of the activity of NF-κB in the cells and genetic variations in TNFAIP3 may be implicated in the risk of systemic lupus erythematosus (SLE) development.Objective The purpose of this paper is to evaluate TNFAIP3 gene polymorphism in SLE and its relationship with autoimmune parameters.Methods The study was carried out on 94 children suffering from SLE and 94 healthy controls of matched age and sex. TNFAIP3 polymorphism by RT-PCR using TaqMan assay, and levels of serum antinuclear and serum anti-double-stranded DNA were measured by ELISA technique. Complement C3 and C4 were estimated by using turbidimetric assay.Results The results showed that there is no significant correlation of TNFAIP3 alleles or genotypes with risk of development of SLE (P>0.05). In addition, the authors did not detect any significant correlation between alleles or genotypes of TNFAIP3 with SLE clinical features and immune disorders (P>0.05).Conclusion The authors concluded that TNFAIP3 polymorphism is not associated with SLE risk. In addition, these results suggested no significant association between the TNFAIP3 SNP and autoimmune parameters, or any complications among SLE individuals.

LONG AND VERY LONG FATTY ACID FRACTIONATION IN SYSTEMIC LUPUS ERYTHEMATOSUS IN THE ACTIVE AND INACTIVE STATUS

Objective: Flare in Systemic Lupus Erythematosus (SLE) is an exacerbation of SLE clinical features that were earlier quiescent. The disease activity changes from inactive to active with an increase of several immunological profiles; the rise of immune activity induces a metabolic shift in SLE patients. The previous study aimed to investigate the long and very long fatty acid fractions (LCFA and VLCFA) in the active and inactive statuses of SLE patients and showed there were dynamic changes in fatty acid fractions in SLE patients, compared to healthy subjects. The aim of this preliminary study is to investigate LCFA and VLCFA in the active and inactive condition of SLE patients.&#x0D; Methods: Four serum samples of active and inactive statuses from the same SLE patients were used in this study. Serum LCFA and VLCFA fractions were analyzed by a 7890 Gas Chromatography (GC) System 5977 Mass Selective Detector (MSD).&#x0D; Results: All of the LCFA and VLCFA fractions were increased in the active condition, compared to SLE patients in inactive, although they were statistically not different (p&gt;0.05). The total fatty acid fraction was 38% higher in active condition compare to inactive. The prominent increase of fatty acid fractions was alpha-linolenic acid (inactive vs. active: 23.25±17.97 vs 48.25±38.58 μmol/l), oleic acid (1300±190.4 vs 1774±866.3 μmol/l) and myristic acid (31.25±12.76 vs 59.25±40.4 μmol/l).&#x0D; Conclusion: The serum of LCFA and VLCFA fractions in SLE patients tend to increase in active conditions.

Clinical features and expression of type I interferon-inducible genes in systemic lupus erythematosus patients harboring rs1143679 polymorphism in China: a single-center, retrospective study.

This case-control study aimed to analyze the clinical features and determine the expression of type I interferon-induced genes in systemic lupus erythematosus (SLE) patients harboring the CD11b rs1143679 single-nucleotide polymorphism (SNP) and elucidate whether it is involved in the relapses of SLE. One hundred twenty-five relatively inactive SLE patients with SLEDAI scores < 6, including 102 CD11b rs1143679 G allele patients as controls and 23 rs1143679 A allele carriers as cases, were enrolled from the SLE patient specimen bank in the Department of Rheumatology and Immunology. The sample set was retrospectively analyzed for differences in clinical features, and quantitative PCR and Western blot analyses were performed to evaluate the relative expression of type I interferon (IFN)-inducible genes. The 24-h urinary protein levels in the case group were significantly elevated, and serum C3 levels were significantly reduced compared with those in the control group (P = 0.019 and P = 0.021, respectively). The relative mRNA levels of IFN-inducible genes IFIT1, IFIT4, and ISG15 in the case group were higher than that in the control group (P = 0.0257, 0.0344, and 0.0311, respectively) and matched with the Western blot results. The relative expression of type I IFN-inducible genes in inactive SLE patients harboring the CD11b rs1143679 polymorphism was higher than that in other lupus patients. These findings suggest that the rs1143679 SNP can precipitate relapses in inactive SLE patients. • The rs1143679 GA genotype was associated with SLE clinical features. • The rs1143679 GA genotype showed higher interferon-inducible gene expression relative to the GG genotype.

Polymorphisms of BLK are associated with renal disorder in patients with systemic lupus erythematosus.

Previous studies are inconclusive on the relationships between BLK gene polymorphisms and clinical features of systemic lupus erythematosus (SLE). The present study aimed to estimate association between BLK loci and SLE clinical features in Chinese population. Associations between BLK single-nucleotide polymorphisms (SNPs) and susceptibility to SLE in this study were estimated using data of 1205 health controls previously reported in the same population. And a total of 814 SLE patients recruited from two different sources according with ACR criteria were analyzed for genotype-phenotype associations. A meta-analysis was conducted of the associations between BLK loci and renal disorder in SLE. The expression quantitative trait locus (eQTL) data were also extracted from the public databases for the selected SNPs. Significant associations were observed between these SNPs and susceptibility to SLE. In addition, the data showed that rs2618479 and rs7812879 were associated with renal disorder [OR = 1.51 (95% CI: 1.15, 1.99) and 1.61 (95% CI: 1.21, 2.14), Pcorr = 0.033 and 0.011, respectively] and proteinuria [OR = 1.47 (95% CI: 1.12, 1.95) and 1.52 (95% CI: 1.14, 2.03), Pcorr = 0.048 and 0.040, respectively]. The consistent associations were observed in two independent centers as well as new cases group. The result of meta-analysis for rs2618479 was also significant [OR = 1.35 (95% CI: 1.12, 1.62)]. In addition, bioinformatics analysis demonstrated that the two SNPs were significantly associated with the expression of BLK in whole blood and several immune cells. Our data support that variant loci of BLK are associated with presence of renal disorder in patients with SLE.

Debut de lupus eritematoso sistémico en paciente masculino

Introducción: El lupus eritematoso sistémico (LES) es una enfermedad multisistémica inflamatoria crónica y autoinmune que produce anticuerpos antinucleares, misma que es capaz de afectar cualquier órgano, su prevalencia es mayor en las mujeres sobre todo en edad fértil que en hombres con una relación 9:1. Su presentación clínica es insidiosa y variable desde lesiones cutáneas típicas como el eritema malar hasta alteraciones sistémicas cardíacas, pulmonares o renales. Su diagnóstico se enfoca en la clínica más la determinación de Anticuerpos antinucleares y de varios anticuerpos y exámenes de laboratorio, así como de imagen para determinar la presencia de otras complicaciones.&#x0D; Objetivo: Aplicar los conocimientos teóricos del Lupus eritematoso sistémico para analizar el caso clínico del debut de un paciente masculino de 60 años.&#x0D; Material y métodos: Estudio descriptivo retrospectivo, presentación de caso clínico.&#x0D; Resultados: Se presenta un caso clínico de un paciente masculino de 60 años de edad que presentó un síndrome coronario agudo, acompañado de lesiones dérmicas y pérdida de peso que después de varias sospechas diagnósticas se confirmó el diagnóstico de LES.&#x0D; Conclusiones: A pesar de la prevalencia más frecuente del LES en mujeres jóvenes; esta patología puede presentarse en varones mayores de 50 años y su sospecha diagnóstica debe estar presente en pacientes que presenten características clínicas insidiosas de LES ya que su diagnóstico temprano puede evitar las complicaciones sistémicas que esta patología puede desarrollar si no se da el tratamiento adecuado

Association study between X-linked susceptibility genes and clinical features in Chinese female patients with systemic lupus erythematosus

Recent large-scale genetic association studies have identified that several single nucleotide polymorphisms (SNPs) on X chromosome are correlated with risk of systemic lupus erythematosus (SLE) in Chinese population. The aim of this study was to estimate association between these loci and clinical features in female patients with SLE. Six SNPs identified in previous studies were genotyped. Odds ratio (OR) was calculated with adjusting for potential confounding factors. A total of 772 SLE patients were included in the final analysis. The data showed that 3 SNPs (rs5914778, rs3853839 and rs1059702) were marginally associated with several clinical subphenotypes. Furthermore, consistent associations were also found in two independent cohorts. However, the cumulative genetic risk score (GRS) was not associated with clinical manifestations as well as the disease activity index at disease diagnosis. In summary, genetic variants in X-linked genes may be potentially associated with presence of specific clinical feature. Further studies in distinct ethnical populations are required to clarify the association between these loci and presence of SLE clinical features.

Diagnostic potential of metastasis-associated-lung-adenocarcinoma-transcript-1 (MALAT-1) and TNFα and hnRNPL related immunoregulatory long non-coding RNA (THRIL) in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo determine expression levels and diagnostic value of metastasis-associated-lung-adenocarcinoma-transcript-1 (MALAT-1) and TNFα and hnRNPL related immunoregulatory long non-coding RNA (THRIL) in systemic lupus erythematosus (SLE), and to assess their role in the clinical characteristics of SLE and disease activity. Patients and methodsStudy included 40 patients with SLE and 30 matched controls. SLE Disease Activity Index (SLEDAI) score was assessed. Expression levels of MALAT-1 and THRIL were detected in the serum by using Real-time polymerase chain reaction and 2−ΔΔCT method. ResultsMean age of patients was 40.1 ± 9 years (25–55 years), they were 38 females and 2 males and disease duration was 16.5 ± 3.9 years. Their mean SLEDAI was 5.8 ± 5.3. Expression levels of MALAT-1 and THRIL were found to be significantly upregulated in the serum of SLE patients compared with controls (set as 1). MALAT-1 fold change = 3.7 ± 3.8 (p = 0.009), and THRIL fold change = 3.6 ± 3.4 (p = 0.026). There were significant correlations between MALAT-1 with THRILL (r = 0.44, p = 0.005), proteinuria (r = 0.45, p = 0.006), erythrocyte sedimentation rate (r = 0.43, p = 0.006) and SLEDAI (r = 0.36, p = 0.024). No significant correlations were found between THRIL and study parameters. Sensitivity and specificity of MALAT-1 and THRIL were determined (sensitivity 67.5% and 65% respectively), (specificity 100% for both, total accuracy 80% and 81.4% respectively), and the combined effect of both increased sensitivity and total accuracy to 70% and 82.9% respectively. THRIL was a significant predictor for SLE disease (p = 0.02). ConclusionMALAT-1 and THRIL may be potential diagnostic biomarkers for SLE and only MALAT-1 may be valuable in detecting disease activity.

Association of Abnormal Elevations in IFIT3 With Overactive Cyclic GMP-AMP Synthase/Stimulator of Interferon Genes Signaling in Human Systemic Lupus Erythematosus Monocytes.

Increasing evidence indicates that the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) signaling pathway has a critical pathogenic role in systemic lupus erythematosus (SLE). Expression levels of the interferon (IFN)-inducible gene IFIT3 are elevated in SLE patients. However, it is still not clear how IFIT3 contributes to the pathogenesis of SLE. This study was undertaken to investigate the activation of the cGAS/STING signaling pathway in human SLE monocytes, and to determine how elevated expression of IFIT3 could contribute to overactive cGAS/STING signaling in patients with SLE. Monocytes from SLE patients or healthy controls were examined for activity of the cGAS/STING signaling pathway and expression levels of IFIT3. Correlations between cGAS/STING signaling activity and SLE clinical features were analyzed. Gain- or loss-of-function experiments were used to determine the role of IFIT3 in cGAS/STING signaling. Coimmunoprecipitation assays were used to identify the interaction between IFIT3 and other proteins. The cGAS/STING signaling pathway was found to have enhanced activity in monocytes from SLE patients compared to healthy controls, as indicated by the higher expression of IFNβ downstream. Levels of IFIT3 were significantly elevated in human SLE monocytes, and this was positively correlated with the activity of the cGAS/STING signaling pathway. In vitro, the expression of VACV70-induced IFNβ was reduced by knockdown of IFIT3, whereas overexpression of IFIT3 produced an opposite effect. Finally, IFIT3 was found to interact with both STING and TANK-binding kinase 1. These findings suggest that IFIT3 is one of the genes that contributes to the overactive cGAS/STING signaling pathway in human SLE monocytes. IFIT3 may therefore serve as a novel therapeutic target for blocking the production of type I IFN and other proinflammatory cytokines by the cGAS/STING signaling pathway in patients with SLE.

From Childhood to Adulthood: The Trajectory of Damage in Patients With Juvenile-Onset Systemic Lupus Erythematosus.

To determine the longitudinal damage trajectory of patients with juvenile-onset systemic lupus erythematosus (SLE), and to identify baseline and disease course predictors of damage trajectory. This is a retrospective inception cohort. Longitudinal pediatric-age data were obtained from a juvenile-onset SLE research database, while adult-age data were obtained from either a research database or patients' charts. Baseline factors were tested as predictors. Time-varying factors were lagged 6-24 months before a visit for testing their predictive effects. The longitudinal damage trajectory was modeled using a weighted generalized estimating equation. This study cohort consisted of 473 subjects, with followup to 26 years. A total of 65% of patients were ages >18 years at last followup. Cataracts (14%), avascular necrosis (10%), and osteoporosis (5%) were the most common items of damage. Two patients had myocardial infarctions. Baseline features, self-reported ethnicity (Afro-Caribbean), earlier time periods of diagnosis, and the presence of a life-threatening major organ manifestation (lupus nephritis class III-V, cerebrovascular accidents, major organ vasculitis, pulmonary hemorrhage, or myocarditis), were associated with greater damage. Throughout the disease course, an acute confusional state, lupus headache, and fever predicted subsequent increases in the damage trajectory. A higher prednisone dose and exposure to cyclophosphamide also predicted subsequent increases in the damage trajectory. Antimalarial exposure was protective against an increase in damage trajectory. Patients with juvenile-onset SLE accrue damage steadily into adulthood. Baseline factors predict greater damage and/or influence the evolution of the damage trajectory. Additionally, SLE clinical features and therapies during the course of disease predict additional changes in the damage trajectory.